Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003090 (arthrodesis)
 8,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although there is considerable interest in the use of bone morphogenetic protein (BMP) to promote periodontal regeneration, little is known of its effects on the early stages of wound healing. The aim of this study was to investigate the effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) on an early stage of post-operative wound healing and following complete healing (10 and 38 days, respectively) in a rat model of periodontal regeneration. The buccal aspects of molar roots were carefully denuded of their periodontal ligament through a bony window created in the mandibles of Wistar rats under general anesthesia. After the root surfaces were acid-conditioned, a 10-microL quantity of 50 microg/mL rhBMP-2 in a collagen gel solution was placed into the surgically created defect in test animals; in controls, either a 10-microL quantity of only collagen gel was received, or the defect was untreated. Animals were killed 10 days or 38 days after surgery and the tissues processed for histological examination. Transverse 5-microm sections were stained for the identification of new bone, cementum, and collagen fiber formation. In the 10-day study groups, new bone formation over the second molar and beyond the defect was significantly increased in the test group (p < 0.02), although there was no evidence of increased ankylosis. RhBMP-2 stimulated more than twice the area of cementum growth coronally compared with controls (712 +/- 286 microm2 and 258 +/- 57 microm2, respectively). Connective tissue attachment, including the number and width of collagen bundles, was similar in both test and controls. Complete healing without any evidence of ankylosis had occurred in all animals 38 days post-operatively, and no significant differences were observed between test and control groups. In conclusion, a single dose of rhBMP-2 increased the rate of normal intramembranous bone formation and selectively enhanced cementum formation coronally during early wound healing. However, the finding that rhBMP-2 induced bone formation at some distance from the defect suggests the importance of developing a suitable delivery system to maintain the concentration of BMP-2 at the site of implantation for potential therapeutic use.
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PMID:Recombinant human bone morphogenetic protein-2 promotes wound healing in rat periodontal fenestration defects. 924 Mar 82

A prospective animal study of posterolateral lumbar spine arthrodesis was performed to determine the temporal and spatial pattern of gene expression and to determine the effect of recombinant human bone morphogenetic protein 2 on the gene expression pattern of a healing spine fusion mass. In Group 1, 20 adult New Zealand rabbits underwent L4-L5 posterolateral intertransverse process arthrodesis using autograft alone. Two rabbits were euthanized at each of the following points: 0, 2, and 4 days, and 1, 2, 3, 4, 5, 6, and 10 weeks after surgery. The same surgical technique was used for 16 rabbits in Group II, except that the autograft first was soaked in a solution of recombinant human bone morphogenetic protein 2 before implantation. Ribonucleic acid was extracted from different regions of the fusion mass at each point and analyzed for expression of bone and cartilage related genes using reverse transcription polymerase chain reaction. A reproducible temporal sequence and spatial pattern of gene expression was found in healing spine fusions. In the central portion of the fusion mass a temporal lag in gene expression was observed that parallels the lag in healing within the central zone previously observed in histologic studies. Treatment of bone graft with recombinant human bone morphogenetic protein 2 resulted in an increase in the early expression of bone morphogenetic protein 6 which was associated with expression of higher levels of Type I collagen, osteocalcin, and other bone related genes. These findings suggest that central nonunion may be associated with delayed expression of osteoblast related genes in the central region of the forming fusion mass. The growth factor, recombinant human bone morphogenetic protein 2, increased the level of bone related gene expression throughout the fusion mass, eliminated the delay in healing within the central zone, and may decrease the likelihood of a nonunion.
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PMID:The Marshall R. Urist Young Investigator Award. Gene expression during autograft lumbar spine fusion and the effect of bone morphogenetic protein 2. 964 69

The influence of gamma-ray irradiation on a cementum-impregnated gelatine membrane (CGM) was analyzed with emphasis on its function during periodontal regeneration. In brief, proteins were extracted from gamma-ray irradiated cementum (gammaC). With the gammaC protein, sample cells (gingival fibroblasts, periodontal ligament cells, and alveolar bone cells) were co-cultured, and cytological parameters (cell attachment, cell differentiation and alkaline phosphatase activity) were analyzed. Additionally, kinetics of some gene expression was analysed using reverse transcript RT-PCR, which included osteoproteogerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) mRNA. BMP-2 and osteonectin were resistant to gamma-rays, and other cytokines involved in regeneration were decreased. Thus, the attachment activity of osteoblasts to gammaC protein was higher than that of non-irradiated cementum (control C). The expression of OPG/OCIF mRNA was lower in co-cultured cells with gammaC protein than those with in control C protein. Together the results imply that some cytokine in intact cementum prevents the attachment (differentiation) of bone cells onto the root surface, which may explain why the introduction of CGM following gingival flap surgery induces new cementum, new ligament and new bone formation, but CGM irradiated with gamma-rays for clinical use causes ankylosis.
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PMID:Effects of irradiation on cementum matrix cytokins function during periodontal regeneration. 1514 42

We report the case of a girl presenting with an unusual form of multiple joint fusion. Skeletal abnormalities consisted of radioulnar synostosis and vertebral fusions without any carpal, digital or tarsal involvement, and broad ribs and clavicles. Spinal X-rays were available from age 4 to 21, demonstrating that the spinal involvement was progressive and led to a complete anterior and lateral fusion of vertebrae. A complete sequencing of the NOGGIN gene failed to find any mutation. In addition, this girl was carrier of an apparently balanced reciprocal translocation t(10;20)(p11;p13). We investigated the role of the BMP2A gene as a potential candidate gene. Fluorescence in situ hybridization with YAC probes from chromosome 20 showed that the BMP2A gene was not disrupted by the translocation breakpoint.
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PMID:Unusual phenotype with progressive vertebral fusion in a girl with an apparently balanced t(10;20)(p11;p13) translocation. 1573 60

The widespread use of fusion procedures in the management of spinal disorders has led investigators to explore the use of growth and differentiation factors in such procedures. As an adjuvant to allograft bone or as a replacement for harvested autograft, bone morphogenetic proteins (BMPs) appear to improve fusion rates after spinal arthrodesis in both animal models and humans, while reducing the donor-site morbidity previously associated with such procedures. The use of recombinant genetic technology in the production of BMP has improved the efficiency, cost effectiveness, and safety of producing and using such materials. Recombinant human BMP-2 (rhBMP-2), as one of the first factors identified in the process of endochondral bone formation, has been extensively researched over the past decade. The efficacy and dose profile of this differentiation factor in the context of various carrier substrates has been investigated. Based on the encouraging results of preliminary studies, the future role of rhBMP-2 may lie in its replacement of autologous bone grafting and, consequently, the reduced need for instrumented fixation, while concurrently improving overall fusion rates. The authors provide an overview of BMP and review its use in clinical and laboratory settings.
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PMID:Bone morphogenetic protein in spinal fusion: overview and clinical update. 1673 30

Periodontal ligament-associated protein-1 (PLAP-1)/asporin is a recently identified novel member of the small leucine-rich repeat proteoglycan family. PLAP-1/asporin is involved in chondrogenesis, and its involvement in the pathogenesis of osteoarthritis has been suggested. We report that PLAP-1/asporin is also expressed specifically and predominantly in the periodontal ligament (PDL) and that it negatively regulates the mineralization of PDL cells. In situ hybridization analysis revealed that PLAP-1/asporin was expressed specifically not only in the PDL of an erupted tooth but also in the dental follicle, which is the progenitor tissue of the PDL during tooth development. Overexpression of PLAP-1/asporin in mouse PDL-derived clone cells interfered with both naturally and bone morphogenetic protein 2 (BMP-2)-induced mineralization of the PDL cells. On the other hand, knockdown of PLAP-1/asporin transcript levels by RNA interference enhanced BMP-2-induced differentiation of PDL cells. Furthermore co-immunoprecipitation assays showed a direct interaction between PLAP-1/asporin and BMP-2 in vitro, and immunohistochemistry staining revealed the co-localization of PLAP-1/asporin and BMP-2 at the cellular level. These results suggest that PLAP-1/asporin plays a specific role(s) in the periodontal ligament as a negative regulator of cytodifferentiation and mineralization probably by regulating BMP-2 activity to prevent the periodontal ligament from developing non-physiological mineralization such as ankylosis.
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PMID:PLAP-1/asporin, a novel negative regulator of periodontal ligament mineralization. 1752 60

The regeneration of the periodontal attachment apparatus remains clinically challenging because of the involvement of three tissue types and the complexity of their relationship. Human recombinant bone morphogenic protein-2 (rhBMP-2) can accelerate the regeneration of bone and cementum and the insertion of periodontal ligament fibers but may lead to a deranged periodontal relationship, ankylosis and root resorption.This study evaluated a novel approach to regeneration of the periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication-defective adenovirus to express the BMP-2 gene and Pluronic F127 (PF127). Twenty-four periodontal defects were surgically created in 12 New Zealand white rabbits and randomly assigned to three experimental groups with MSCs: the advBMP-2 group; the advbetagal group; the MSC group and one control group: PF127 only. The regenerated periodontal attachment apparatus was assessed histologically and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis.This approach regenerated not only cementum with Sharpey's fiber insertion, but also statistically significant quantities of bone, re-establishing a more normal relationship among the components of the regenerated periodontal attachment apparatus, which is beneficial for the maintenance of periodontal health.Ex vivo gene transfer using stem cells as vectors may provide an advantage of slower BMP-2 release, increasing cementogenesis. There is regeneration of the periodontal attachment apparatus, whereas direct usage of the protein (rhBMP-2) yields unhinged periodontal relationship. Thus, this approach may represent an alternative means for periodontal alveolar bone graft in clinical settings.
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PMID:Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty. 1870 11

A patient who complained of difficulty in opening his mouth after condylar neck fracture 1 year ago presented typical features of temporomandibular joint ankylosis in clinical and radiologic examinations. To demonstrate a possible pathogenesis of temporomandibular joint ankylosis after condylar neck fracture, the fractured condylar portion removed was examined by histologic and immunohistochemical stainings. Interpositional gap arthroplasty was performed by removing the inferomesially displaced fractured condyle, and reconstruction with subcutaneous dermis to the previous vertical height was performed immediately. The fractured condylar portion was almost intact with slight erosion of the condylar cartilage. In the hematoxylin and eosin and Masson trichrome stainings, an extensive chondroid hyperplasia with abundant hyaline cartilage was shown in the removed condylar portion. There were also hyperplastic features of the synovial membrane, which were abnormally distributed throughout the chondroid tissues. In the immunohistochemical stainings of proliferating cell nuclear antigen (PCNA) and bone morphogenetic protein (BMP)-2 and BMP-4, the chondroid tissues were conspicuously hyperplastic and strongly positive for BMP-4 but sparse for BMP-2. From these results, we think that the hyperplastic chondroid tissue was derived from the callus of the primary fractured site of the condylar neck and propose that the chondroid tissue could proliferate continuously because of synovial tissue support from around the temporomandibular joint, resulting in temporomandibular joint ankylosis. This pathogenesis is quite different from those of other diaphyseal fracture of long bones.
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PMID:Temporomandibular joint ankylosis caused by chondroid hyperplasia from the callus of condylar neck fracture. 1916 36

Over one million fractures occur per year in the US and are associated with impaired healing increasing patient morbidity, stress, and economic costs. Despite improvements in surgical technique, internal fixation, and understanding of biologics, fracture healing is delayed or impaired in up to 4% of all fractures. Complications due to impaired fracture healing present therapeutic challenges to the orthopedic surgeon and often lead to chronic functional and psychological disability for the patient. As a result, it has become clinically desirable to augment mechanical fixation with biologic strategies in order to accelerate osteogenesis and promote successful arthrodesis. The discovery of bone morphogenic protein (BMP) has been pivotal in understanding the biology of fracture healing and has been a source of intense clinical research as an adjunct to fracture treatment. Multiple in vitro and in vivo studies in animals have elucidated the complex biologic interactions between BMPs and cellular receptors and have convincingly demonstrated rhBMP-2 to be a safe, effective treatment option to enhance bone healing. Multiple clinical trials in trauma surgery have provided level 1 evidence for the use of rhBMP-2 as a safe and effective treatment of fractures. Human clinical trials have provided further insight into BMP-2 dosage, time course, carriers, and efficacy in fracture healing of tibial defects. These promising results have provided hope that a new biologic field of technology has emerged as a useful adjunct in the treatment of skeletal injuries and conditions.
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PMID:Recombinant human bone morphogenetic protein-2 in the treatment of bone fractures. 1970 67

Human recombinant bone morphogenetic protein 2 (rhBMP-2) accelerates bone regeneration but is associated with limited cementum and periodontal ligament regeneration, local root resorption, and ankylosis. This study assessed a new approach to the regeneration of the alveolar bone and periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication defective adenovirus to express the BMP-2 gene and pluronic F127 (PF127) in a large mammalian animal model. Bilateral maxillary periodontal defects were created over the premolar area in 9 mature male miniature swine. The 18 defects were randomly assigned to receive either BMP-2-expressing MSCs in the advBMP-2 group or MSCs alone in the MSC group. The regenerated periodontal attachment apparatus was evaluated histologically, and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis. Three months after implantation, significant bone volume was regenerated in the advBMP-2 group. Periodontal apparatus regeneration was significantly better in the advBMP-2 group. New cementum and Sharpey fibers were observed on the denuded root surfaces in the advBMP-2 group, whereas incomplete healing with localized root surface resorption was noted in the control group. The use of ex vivo BMP-2-engineered autologous MSCs enhanced bone and periodontal apparatus regeneration in maxillary alveolar and periodontal defects in swine. This novel integrated approach might be suitable for clinical periodontal apparatus repair. This may be an alternative for cleft alveolar bone graft surgery.
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PMID:Engineered autologous bone marrow mesenchymal stem cells: alternative to cleft alveolar bone graft surgery. 2297 60


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